Analysis of transcriptional profiles and functional clustering of global cerebellar gene expression in PCD3J mice.
The Purkinje cell degeneration (PCD) mutant mouse is characterized by a degeneration of cerebellar Purkinje cells and progressive ataxia. To identify the molecular mechanisms that lead to the death of Purkinje neurons in PCD mice, we used Affymetrix microarray technology to compare cerebellar gene expression profiles in pcd3J mutant mice 14 days of age (prior to Purkinje cell loss) to unaffected littermates. Microarray analysis, Ingenuity Pathway Analysis (IPA) and expression analysis systematic explorer (EASE) software were used to identify biological and molecular pathways implicated in the progression of Purkinje cell degeneration. IPA analysis indicated that mutant pcd3J mice showed dysregulation of specific processes that may lead to Purkinje cell death, including several molecules known to control neuronal apoptosis such as Bad, CDK5 and PTEN. These findings demonstrate the usefulness of these powerful microarray analysis tools and have important implications for understanding the mechanisms of selective neuronal death and for developing therapeutic strategies to treat neurodegenerative disorders.
Ford
Gregory D
GD
Department of Neurobiology and Neurotoxicology, Meharry Medical College, Nashville, TN 37208, USA; Department of Anatomy and Neurobiology, Morehouse School of Medicine, 720 Westview Drive, SW, MRC 223, Atlanta, GA 30310, USA. Electronic address: bford@msm.edu.
Ford
Byron D
BD
Department of Anatomy and Neurobiology, Morehouse School of Medicine, 720 Westview Drive, SW, MRC 223, Atlanta, GA 30310, USA.
Steele
Ernest C
EC
Department of Anatomy and Neurobiology, Morehouse School of Medicine, 720 Westview Drive, SW, MRC 223, Atlanta, GA 30310, USA.
Gates
Alicia
A
Department of Anatomy and Neurobiology, Morehouse School of Medicine, 720 Westview Drive, SW, MRC 223, Atlanta, GA 30310, USA.
Hood
Darryl
D
Department of Neurobiology and Neurotoxicology, Meharry Medical College, Nashville, TN 37208, USA.
Matthews
Mika A B
MAB
Department of Anatomy and Neurobiology, Morehouse School of Medicine, 720 Westview Drive, SW, MRC 223, Atlanta, GA 30310, USA.
Mirza
Sophia
S
Department of Anatomy and Neurobiology, Morehouse School of Medicine, 720 Westview Drive, SW, MRC 223, Atlanta, GA 30310, USA.
MacLeish
Peter R
PR
Department of Anatomy and Neurobiology, Morehouse School of Medicine, 720 Westview Drive, SW, MRC 223, Atlanta, GA 30310, USA.
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D020869:Gene Expression Profiling; D051379:Mice; D008817:Mice, Mutant Strains; D020411:Oligonucleotide Array Sequence Analysis; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism*; D014158:Transcription, Genetic